Dr. Sonia Lupien showing how salivary cortisol is collected PHOTO: OWEN EGAN

Stress linked to memory loss

BRONWYN CHESTER | At promptly 5 pm, Easter Monday, Sonia Lupien's phone began to ring. The news media embargo was off her Nature Neuroscience (May 1998) article on stress and memory and the newsmakers were anxious to tell the world that "yes, there is a relationship between stress and memory impairment, at least in the elderly." Reuters and Associated Press news agencies called and ABC radio claimed, over the phone: "We're on the air. Do you want to talk to us?" Radio stations from Germany, Switzerland and the United Kingdom were next. More recently, an American women's health magazine interviewed the 32-year-old neuropsychologist and assistant professor of psychiatry. "They wanted to extrapolate to women at work, so I gave them the definition of stress [a new and unexpected event where the individual lacks a sense of control] so that they wouldn't cause women more stress," laughs Lupien, emphasizing that one cannot extrapolate from an aging population to a younger one. Curiously, Canadian media have shown virtually no interest in the story. Only La Presse reported the study and that was just a reprint of an Agence France Presse item. "I guess people in Canada are not that stressed," concludes Lupien with a chuckle, adding that she is mainly interested in having her work presented in magazines targeted at older readers. That's because the elderly are not only her subjects, they are the people she hopes to help with her research findings. The Nature Neuroscience article points to a clear connection between cortisol -- a hormone produced in the body in response to stress -- and memory loss in elderly research subjects. Lupien and her research associates found that approximately one third of the 51 healthy subjects who took part in the study -- their average age was 73 -- suffered from sustained high levels of cortisol over a five-year period. This group displayed poor memory recall when asked to remember images they had been shown 24 hours earlier. These individuals also took longer to find their way through a maze (specially designed by Université de Montréal architect Romedi Passini to measure spatial memory), as compared to other research subjects with moderate but increasing levels of cortisol or moderate and decreasing levels. The subjects who had moderate or low and decreasing levels of cortisol had less difficulty with both tasks. Magnetic resonance imaging (MRI), a scan which visualizes the brain, showed that the same high-cortisol group had hippocampi 14% smaller than those in the low or moderate cortisol groups. None of which surprised Lupien, for it confirmed what is known in animal studies: high and sustained cortisol levels atrophy the hippocampus, a part of the brain involved in memory. However, said Lupien in an interview in her office at the Douglas Hospital-McGill University Research Centre, hippocampal atrophy may not last forever. In rats, for instance, the use of anti-depressants like Prozac decreases cortisol levels and "we've seen that hippocampal damage is reversible." (Rats stressed for three weeks suffered hippocampal atrophy but when left alone for a week, that part of the brain returned to normal size.) All of which leads Lupien to wonder about the relationship between depression, cortisol levels and the onset of such dementias as Alzheimer's disease. It is not uncommon, she said, for elderly people to suffer from depression and experience the resultant memory impairment. Lupien worries that many healthcare workers don't consider depression in the elderly, thinking that old age is a time of serenity. When symptoms of memory loss crop up, Lupien wonders if the medical community is a little too quick in diagnosing Alzheimer's. "Given the new anti-Alzheimer drugs, physicians may be tempted to treat such patients for Alzheimer's rather than first considering depression," she says. "I say: Start with depression treatment, then, if necessary, start with the Alzheimer's. Start with the positive." Not that she's advocating more medication for an already overmedicated sector of the population. Lupien says, "You can cure with a pill or you can cure with social policies." There are few programs offering psychotherapy for the elderly, for instance. Fortunately, Lupien is in a situation where she works closely with the physicians of her subjects and can make recommendations about their care. "I have a big mouth so I speak to a lot of people. This is a rare situation where we work closely with physicians." Recently, for instance, Lupien recommended treatment for depression for a 78-year-old woman who was showing serious impairment in memory recall tests. "I had to phone her four times per day to remind her to do her cortisol measurements. The trouble was she couldn't remember my name. So I had to create a game which would require her to use her implicit memory." Implicit or unconscious memory involves making associations of one's own creation, a process not controlled by the hippocampus and, therefore, unaffected by a damaged hippocampus as opposed to explicit memory, an association already made by an outside source -- like the name Sonia, for instance -- which is controlled by the hippocampus and therefore irretrievable if that part of the brain has atrophied. Lupien asked the patient to choose a name for her and she became "your friend Michèle." Since then, Lupien has had the subject's brain scanned with MRI, a procedure she will repeat after the woman has completed a six-week course of anti-depressants, in order to see if there are changes in the hippocampus. Lupien's ultimate aim is ambitious. As her understanding of the relationship between cortisol, memory, depression and dementia is refined, Lupien hopes, one day, to contribute to preventing certain types of memory loss and dementia. She clearly enjoys old people. She instructs her graduate students to respect elderly people and to give them an hour for every hour they give to research. It is from those informal hours spent chatting with her subjects that she has learned that aging is not necessarily a serene time of life. There may be the stress associated with loss of friends and loved ones, the loneliness resulting from children moving away and the frustration of reduced mobility, vision, hearing and, all too often, income. Though she doesn't have an explanation for her attachment to old people other than musing about having "lived long in another life," Lupien finds that she "connects very well with them. I feel most comfortable with them, there are fewer barriers." Once, for instance, Lupien invited a "sad-looking" elderly man sitting in a shopping plaza to sit down for a coffee. "I talked to him for three hours. He told me all about the wooden sidewalks of his childhood and how it was dangerous to walk on them in the spring because all the nails would be sticking out. They have those wonderful stories to tell." Lupien regrets that so few people like to work with the elderly. The relationship between stress, memory, depression and dementia, for instance, is studied only by her and some German researchers -- two of whom are graduate students working with Lupien. She is often moved by the seriousness with which old people will do a job when it is asked of them. Once, for instance, Lupien asked her 88-year-old, near-blind grandmother, Adrienne Lupien, to come up with five songs for each of three periods of her life: childhood, young motherhood and at age 65, which the researcher wanted to use in some preliminary research on music and memory. "She would call me up at 5:15 a.m. to tell me that she had thought of another. She took it very seriously." Among the 10 old people in Mme. Lupien's residence, the saddest memories elicited by the songs were those from the era when they were 65.